Engineering Research Center of North-East Cold Region Beef Cattle Science & Technology Innovation, Ministry of Education, Yanbian University, No.977 Park Road, Yanji, 133002, People's Republic of China.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido, 080-8555, Japan.
Parasitol Res. 2023 Mar;122(3):781-788. doi: 10.1007/s00436-022-07771-6. Epub 2023 Jan 4.
Neospora caninum is a protozoan parasite which can infect a range of animals, including dogs, cattle, and sheep. Bovine neosporosis, which mainly causes abortion in cattle, results in substantial economic losses worldwide. To study the effects of N. caninum infection on the placenta, a pregnant mouse model for N. caninum infection was established. The litter size (8.6 ± 1.5) and the number of live pups (6.4 ± 1.8) of infected dams were significantly lower compared with those of non-infected dams. Trophoblast cell shrinkage and a large number of apoptosomes were detected in the placentas of the infected group. The parasite load in the placental tissue was significantly higher with time after infection. Likewise, apoptosis of placental trophoblast cells significantly increased with time after infection. Among the 66 apoptotic genes detected in this study, eight genes, including Bcl-2, were significantly differentially expressed by about > tenfold in infected and uninfected mice. The expression of BAX and tumor necrosis factor-alpha (TNF-α) was upregulated in the placental cells of the infected mice, whereas the expression of BCL-2 was downregulated. Enzyme-linked immunosorbent assays (ELISAs) showed that apoptotic protease caspase-3 level was significantly increased in placental cell suspension, and insulin-like growth factor (IGF)-2 level was significantly reduced. Acetylcholine (ACH) and placental prolactin (PL) levels were initially decreased but eventually increased. In summary, infection of mice with N. caninum caused apoptotic damage to the placental tissues, cells, and genes and affected the normal physiological functions of placenta, which may largely explain the adverse pregnancy outcomes caused by N. caninum infection in mice.
刚地弓形虫是一种可以感染包括犬、牛和羊在内的多种动物的原生动物寄生虫。牛新孢子虫病主要导致牛流产,在世界范围内造成了巨大的经济损失。为了研究刚地弓形虫感染对胎盘的影响,建立了刚地弓形虫感染的怀孕小鼠模型。与未感染的对照组相比,感染组的产仔数(8.6±1.5)和活仔数(6.4±1.8)显著降低。感染组胎盘的滋养层细胞收缩,凋亡小体大量出现。感染后胎盘组织中的寄生虫载量随时间显著增加。同样,感染后胎盘滋养层细胞的凋亡也随时间显著增加。在本研究检测到的 66 个凋亡基因中,包括 Bcl-2 在内的 8 个基因在感染和未感染的小鼠中差异表达约 10 倍以上。感染小鼠胎盘细胞中 BAX 和肿瘤坏死因子-α(TNF-α)的表达上调,而 BCL-2 的表达下调。酶联免疫吸附试验(ELISA)显示,胎盘细胞悬液中凋亡蛋白酶 caspase-3 水平显著升高,胰岛素样生长因子(IGF)-2 水平显著降低。乙酰胆碱(ACH)和胎盘催乳素(PL)水平最初降低,但最终升高。总之,刚地弓形虫感染导致胎盘组织、细胞和基因发生凋亡损伤,影响胎盘的正常生理功能,这可能在很大程度上解释了刚地弓形虫感染在小鼠中引起的不良妊娠结局。